A native of Tonga, Lotulelei attended Bingham High School in South Jordan, Utah. Playing defensive lineman at 240 pounds, he helped the team to a 14–0 record and a state title in 2006. Lotulelei registered 72 tackles and seven sacks as a senior.

Lotulelei then took the 2009 season off to preserve another year of college eligibility. He was still recruited by BYU, but also Oregon State, Utah State, and Utah. "The Utah coaches came down to Snow a couple of times," Lotulelei said. "They showed me they really wanted me. It showed me they really cared. So coming here wasn't that hard of a choice."[6]

In 2010, Lotulelei arrived at the University of Utah, and played in all 13 games for the Utah Utes football team, and became a starter for the final three games of the season. He totaled 21 tackles with 2.5 tackles for a loss, and also was credited for a half quarterback sack, which came against San Jose State in arguably his best game of the season (season-high five tackles). Lotulelei also made several appearances at offensive guard.

A regular starter in 2011, Lotulelei was an All-Pac-12 Conference performer and won the Morris Trophy as the league's best defensive lineman. He started all 13 games, and registered 44 tackles, 1.5 sacks, one pass breakup, a forced fumble and a fumble recovery. His 9.0 tackles for loss tied sophomore linebacker Trevor Reilly for second on the team. In a 14–31 loss against Washington, Lotulelei had six tackles including 2.5 tackles for a loss. A week later he had five tackles in a 14–35 loss against Arizona State. Against California, Lotulelei surprised with a 17-yard reception on a fake punt play. Utah finished the regular season 7–5 and played Georgia Tech in the 2011 Sun Bowl. Lotulelei made six tackles and recovered a fumble and was named the Bowl's Most Valuable Lineman.[8]

Lotulelei returned to Utah for his senior year, and started in all 12 games at nose tackle. He recorded 42 tackles included a team-high 11 tackles for loss and 5.0 sacks, while also having four pass breakups, four fumble recoveries and three forced fumbles. A season-high seven tackles plus two pass breakup came early in the season in a 24–21 win against the school to which he had previously committed, Brigham Young. Lotulelei blocked a 51-yard field goal attempt with 1 second remaining following a third-down incompletion.[9] Two weeks later, Lotulelei had a heralded performance against All-Pac-12 center Khaled Holmes of the USC Trojans in a 28–38 loss for the Utes.[10]

Forgoing the chance of a professional career in 2012, Lotulelei decided to return to Utah after the 2011 season. In preseason mock drafts from May 2012, Lotulelei was listed as a late first-rounder for the 2013 NFL Draft as well.[11] By mid-season, he had moved up to a top-3 spot.[12] After the season concluded, Lotulelei was still projected to be picked among the first five selections.[13][14] Utah had not seen one of their defensive linemen selected in the first round since Luther Elliss in 1995. Lotulelei's rare combination of power, snap count anticipation, instincts, quickness, and athleticism frequently drew parallels to Haloti Ngata.[15]

All values from Utah Pro Day (March 20, 2013),[16] except for measurements, which are from NFL Combine[17]

Lotulelei was not allowed to work out with the rest of the defensive linemen at the 2013 NFL Scouting Combine after an echocardiogram revealed an abnormally low ejection fraction.[18][19] While a normal heart will pump between 55 to 70 percent of the blood out of the left ventricle of the heart and into the body, Lotulelei's left ventricle was found to be pumping at only 44 percent.[19] After further tests by cardiologists at the University of Utah, Lotulelei's condition found to be caused by a viral infection and eventually disappeared, showing "complete normalization of the heart muscle function." Lotulelei has been cleared "to participate in professional athletics without restrictions."[20]

A month after the combine, Lotulelei worked out in front of NFL personnel at Utah's Pro Day. He reportedly "looked strong in all the position drills," and registered 38 repetitions in the 225-pound bench press,[21] which would have tied him with Margus Hunt and Brandon Williams for the top mark at the combine.[22] But despite being medically cleared, Lotulelei's falsely assumed heart condition tarnished his draft prospects.[23] Early April mock drafts projected him to fall out of the top-10.[24][25] However, Lotulelei and Sharrif Floyd were "generally viewed as the top two [defensive tackles] in this class."[26] Only a week before the draft, Lotulelei moved up to the No. 4 spot, right behind Floyd, in Sports Illustrated's'mock draft.[27] He was drafted in the first round, 14th overall by the Carolina Panthers, as the second defensive tackle selected after Sheldon Richardson.

On May 22, 2013, Lotulelei signed a four-year $9.60 million deal.[28] He was named the starting defensive tackle in the 2013 season. On September 3, 2013, Lotulelei changed his jersey number from 96, to 98. He had his first NFL career sack against the New York Giants.[29] In his rookie year, Lotulelei started all 16 regular games for the Panthers, recording 42 tackles, three sacks and 23 quarterback pressures.[30] He finished 2nd in the NFL in run stop percentage among defensive tackles at 12.9%, was rated by Pro Football Focus as the 6th best defensive tackle against the run, and helped Carolina improve from 14th in the NFL in run defense in 2012 (110.1 yards per game) to second (86.9 yards per game) in 2013.[31][32] The Panthers finished first in the NFL with 60 sacks in 2013, second in points per game, and third in DVOA team defense. Lotulelei finished 4th in AP Defensive Rookie of the Year voting.[33]

Lotulelei picked up from his strong rookie performance in his debut against the Tampa Bay Buccaneers where he recorded 1 quarterback hit, 2 quarterback hurries, and 1 tackle. Through the first week of the season, Lotulelei ranked among the top 10 defensive tackles in the NFL in pass rush productivity.[34] During the final, win-or-go victory over the Atlanta Falcons in the final game of the regular season that catapulted the Panthers to back-to-back NFC South division titles, Lotulelei finished the afternoon with 2 sacks, 1 QB hit, 3 hurries during his pash rush opportunities on Matt Ryan while recording 4 stops on only 9 snaps against the run.[35] For the season, Lotulelei recorded 21 defensive stops. [36]

^"Star Lotulelei dominates at Utah’s pro day, may regain esteemed position after combine diagnosis". Yahoo! Sports. March 20, 2013. Before the heart condition that was diagnosed at the scouting combine, Utah defensive tackle Star Lotulelei was thought by most NFL analysts to be a top-3 pick in the upcoming draft, and top-10 at worst. But it was reported on February 24 that abnormalities seen in his echocardiogram—Lotulelei's left ventricle was pumping at 44 percent efficiency compared with the normal range of 55 to 70 percent. That put his combine drills on the shelf, and his future as a high draft prospect in doubt.